title: Glucose-induced regulation of protein import receptor Tom22 by cytosolic and mitochondria-bound kinases.
abstract: Most mitochondrial proteins are imported by the translocase of the outer mitochondrial membrane (TOM). Tom22 functions as central receptor and transfers preproteins to the import pore. Casein kinase 2 (CK2) constitutively phosphorylates the cytosolic precursor of Tom22 at Ser44 and Ser46 and, thus, promotes its import. It is unknown whether Tom22 is regulated under different metabolic conditions. We report that CK1, which is involved in glucose-induced signal transduction, is bound to mitochondria. CK1 phosphorylates Tom22 at Thr57 and stimulates the assembly of Tom22 and Tom20. In contrast, protein kinase A (PKA), which is also activated by the addition of glucose, phosphorylates the precursor of Tom22 at Thr76 and impairs its import. Thus, PKA functions in an opposite manner to CK1 and CK2. Our results reveal that three kinases regulate the import and assembly of Tom22, demonstrating that the central receptor is a major target for the posttranslational regulation of mitochondrial protein import.
authors.affiliation: Institut für Biochemie und Molekularbiologie, ZBMZ, Universität Freiburg, 79104 Freiburg, Germany; Trinationales Graduiertenkolleg 1478, Universität Freiburg, 79104 Freiburg, Germany; Faculty of Biology, Universität Freiburg, 79104 Freiburg, Germany.
authors.forename: Carolin
authors.initials: C
authors.lastname: Gerbeth
authors.forename: Oliver
authors.initials: O
authors.lastname: Schmidt
authors.forename: Sanjana
authors.initials: S
authors.lastname: Rao
authors.forename: Angelika B
authors.initials: AB
authors.lastname: Harbauer
authors.forename: Despina
authors.initials: D
authors.lastname: Mikropoulou
authors.forename: Magdalena
authors.initials: M
authors.lastname: Opalińska
authors.forename: Bernard
authors.initials: B
authors.lastname: Guiard
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Pfanner
authors.forename: Chris
authors.initials: C
authors.lastname: Meisinger
mesh_terms: D047389:Casein Kinase I / Q000378:metabolism; D047390:Casein Kinase II / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D029701:Saccharomyces cerevisiae Proteins; C090857:TOM22 protein, S cerevisiae; D047389:Casein Kinase I; D047390:Casein Kinase II; D017868:Cyclic AMP-Dependent Protein Kinases; D005947:Glucose